Brain Targeting in MPS-IIIA.
Authors: Sorrentino NC, Fraldi A
Abstract
Mucopolysaccharidosis type IIIA (MPS-IIIA) is a childhood metabolic neuropathology caused by the inherited deficiency of the lysosomal enzyme sulfamidase and is characterized by the accumulation of undegraded glycosaminoglycans in the lysosomes of cells and tissues of affected patients. MPS-IIIA represents one of the most common forms of lysosomal storage disorders (LSDs) and to date there is no cure. Since neurodegeneration is the most relevant pathological feature in MPS-IIIA patients, the treatment of the central nervous system (CNS) lesions represents the goal ...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Combination Therapies for Lysosomal Storage Diseases: A Complex Answer to a Simple Problem.
Authors: Macauley SL
Abstract
Abstract Lysosomal storage diseases (LSDs) are a group of 40-50 rare monogenic disorders that result in disrupted lysosomal function and subsequent lysosomal pathology. Depending on the protein or enzyme deficiency associated with each disease, LSDs affect an array of organ systems and elicit a complex set of secondary disease mechanisms that make many of these disorders difficult to fully treat. The etiology of most LSDs is known and the innate biology of lysosomal enzymes favors therapeutic intervention, yet most attempts at treating LSDs with enzyme replacement strategies f...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Prevention is the Best Therapy: The Geneticist's Approach.
We present our experience using PGD for four Lysosomal storage disorders: Tay Sachs, Gaucher type 1, Hunter and Fabry disease with some of the couples being carriers of more than one genetic disorder. PGD is applicable to most disorders for which the gene and the familial mutation are known and should be presented to couples as an alternative to invasive prenatal testing.
PMID: 27491212 [PubMed - in process] (Source: Pediatric Endocrinology Reviews)
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Juvenile NCL (CLN3 Disease): Emerging Disease-Modifying Therapeutic Strategies.
Authors: Augustine EF, Mink JW
Abstract
Abstract Juvenile Neuronal Ceroid Lipofuscinosis is a lysosomal storage disease characterized pathologically by intracellular accumulation of autofluorescent storage material and neurodegeneration. Caused by mutations in the CLN3 gene on chromosome 16p12, the precise functions of the encoded protein remain unclear. Yet, recent preclinical discovery has established new therapeutic targets in development, including immunosuppressants, anti-inflammatories, and gene replacement therapies. Development of robust clinical trial endpoints appropriate for this poly-symptomati...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy.
Authors: Regier DS, Proia RL, D'Azzo A, Tifft CJ
Abstract
The gangliosidoses are lysosomal storage disorders caused by accumulation of GM1 or GM2 gangliosides. GM1 gangliosidosis has both central nervous system and systemic findings; while, GM2 gangliosidosis is restricted primarily to the central nervous system. Both disorders have autosomal recessive modes of inheritance and a continuum of clinical presentations from a severe infantile form to a milder, chronic adult form. Both are devastating diseases without cure or specific treatment however, with the use of supportive aggressive medical management, t...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Types A and B Niemann-Pick Disease.
Authors: Schuchman EH, Wasserstein MP
Abstract
Two distinct metabolic abnormalities are included under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly, frequent pulmonary infections, and profound central nervous system involvement in infancy. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and progressive alterations of their lungs, but there are us...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis).
Authors: Kohlschütter A, Schulz A
Abstract
CLN2 disease is an inherited metabolic storage disorder caused by the deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). The disease affects mainly the brain and the retina and is characterized by progressive dysfunction of the central nervous system, leading to dementia, epilepsy, loss of motor function and blindness. The classical late infantile type begins at around three years of age with epilepsy and/or a standstill of psychomotor development, followed by a rapid loss of all abilities and death in childhood. A late onset form in a small propo...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Insights into the Pathogenesis and Treatment of Krabbe Disease.
Authors: Bongarzone ER, Escolar ML, Gray SJ, Kafri T, Vite CH, Sands MS
Abstract
Krabbe disease (globoid cell leukodystrophy, GLD) is an inherited disease caused by a deficiency in the lysosomal enzyme galactocerebrosidase (GALC). The major galactosylated lipid degraded by GALC is galactosylceramide. However, GALC is also responsible for the degradation of galactosylsphingosine (psychosine), a highly cytotoxic glycolipid. It has been hypothesized that GALC-deficiency leads to psychosine accumulation that preferentially kills oligodendrocytes in the central nervous system and Schwann cells in the peripheral...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Therapy Development for the Lysosomal Storage Disease Fucosidosis using the Canine Animal Model.
Authors: Fletcher JL, Taylor RM
Abstract
Abstract Fucosidosis (OMIM 23000) is an inherited neurodegenerative lysosomal storage disease caused by a deficiency of the lysosomal hydrolase a-L-fucosidase due to mutations in the FUCA1 gene. Without enzyme-targeted therapy patients rarely survive beyond the first decade of life, and therapy options other than supportive care are limited. Hematopoietic transplants, first developed in the fucosidosis dog model, are the only treatment option available capable of delaying the disease course. However, due to the risks and exclusion criteria of this treatment addition...
Source: Pediatric Endocrinology Reviews - August 8, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Primus-Eugen Mullis, MD (1954-2016).
Authors: Dattani M, Mullis A, Flück CE
PMID: 27464413 [PubMed - in process] (Source: Pediatric Endocrinology Reviews)
Source: Pediatric Endocrinology Reviews - July 29, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Finding a Needle in a Haystack: the Advantages of Liquid Chromatography--Tandem Mass Spectrometry (LC-MS/MS) in Determination of Sex Hormones in Children.
Authors: Hirsh S, Ben-Dor A
Abstract
Determination of steroid sex hormones concentrations in children is very important for diagnosis of a wide range of pubertal, adrenal and sex development disorders. The majority of hormone measurements are carried out using traditional immunoassays, due to their technical simplicity, cost and availability of commercial reagents. But, due to limited specificity and sensitivity, traditional immunoassays often fail to determine low concentration analytes such as sex hormones in pediatric blood. In the last decade, the LC-MS/MS assay has risen as a new player in the analyti...
Source: Pediatric Endocrinology Reviews - July 29, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Role of Nuclear Factor Kappa B (NF- κB) in Growth Plate Chondrogenesis.
Role of Nuclear Factor Kappa B (NF-κB) in Growth Plate Chondrogenesis.
Pediatr Endocrinol Rev. 2016 Jun;13(4):720-30
Authors: De Luca F
Abstract
Abstract Nuclear Factor kappa B (NF-κB) is a group of seven transcription factors. Upon activation by a variety of stimuli, NF-κB translocates to the nucleus and modulates the expression of target genes involved in cell growth, survival, and death. Previous evidence indicates that NF-κB regulates bone growth and development. We have shown that the NF-κB p65 is expressed in the growth plate and facilitates longitudinal bone growth by ...
Source: Pediatric Endocrinology Reviews - July 29, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Persistent M üllerian Duct Syndrome Caused by a Novel Mutation of an Anti-MüIlerian Hormone Receptor Gene: Case Presentation and Literature Review.
Persistent Müllerian Duct Syndrome Caused by a Novel Mutation of an Anti-MüIlerian Hormone Receptor Gene: Case Presentation and Literature Review.
Pediatr Endocrinol Rev. 2016 Jun;13(4):731-40
Authors: Elias-Assad G, Elias M, Kanety H, Pressman A, Tenenbaum-Rakover Y
Abstract
Persistent Müllerian duct syndrome (PMDS) is a rare genetic disorder of male internal sexual development defined as lack of regression of Müllerian derivatives in the 46XY male with normally virilized external genitalia and unilateral or bilateral cryptorchidism. Approximately 85% of all cases are caused ...
Source: Pediatric Endocrinology Reviews - July 29, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
Polymorphism of the IGF-I System and Sports Performance.
Authors: Ben-Zaken S, Meckel Y, Nemet D, Dror N, Eliakim A
Abstract
The potential use genetic polymorphism, and in particularly polymorphism of hormone genes, as tool to predict athletic performance is currently very challenging. Recent studies suggest that single nucleotide polymorphisms in IGF-I and myostatin may be beneficial for endurance and short distance running, and may even be associated with elite performance. Polymorphism in IGF-I receptor may differentiate between the two edges of the endurance-power athletic performance running spectrum suggesting beneficial effects for endurance and prevent f...
Source: Pediatric Endocrinology Reviews - July 29, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
LHX4 Gene Alterations: Patient Report and Review of the Literature.
This report extends the range of phenotypes associated with LHX4 gene mutations. To the best of our knowledge, we are the first to report on congenital myopathy in an LHX4 gene mutation. Forthwith, we offer a comprehensive review of the patients published so far with their clinical and genetic characteristics.
PMID: 27464418 [PubMed - in process] (Source: Pediatric Endocrinology Reviews)
Source: Pediatric Endocrinology Reviews - July 29, 2016 Category: Endocrinology Tags: Pediatr Endocrinol Rev Source Type: research
